This is a proposal to engage in a collaborative research effort designed to carry out basic investigations directed toward an increase in information about mental retardation. The primary aim is to expand our knowledge rather than the development of practical applications, although we will not be blind to useful pragmatism. Specifically, we intend to: (1) explore in a close collaborative and cooperative fashion, areas of developmental biology which are relevant to mental retardation; (2) conduct further basic studies into etiology, pathogenesis, and prevention of mental retardation through the utilization of biomedical technology; (3) make available an attractive milieu for the training of young scientists with similar interests and increasing competence. A group of scientists and teachers primarily interested in biological and biomedical approaches to mental retardation has previously been assembled to form this program project. The direction of the investigation is via a time scale which includes the prenatal, perinatal, and postnatal periods; continues into adolescence and adulthood. The latter period is especially significant in both the disciplines of genetics and human gestational biology. Different levels of study to be undertaken and/or continued include genetics, biochemistry, ultrastructural, biomathematical, pharmacologic, behavioral and clinical. Together, the operatives in this cooperative program will direct their efforts toward a major public health problem.